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橄榄苦苷通过减轻氧化应激来保护脑出血引起的血脑屏障破坏。

Oleuropein protects intracerebral hemorrhage-induced disruption of blood-brain barrier through alleviation of oxidative stress.

机构信息

The Second Affiliated Hospital of Suzhou University, Suzhou, China; The Affiliated Hospital of Guizhou Medical University, Guiyang China.

The Second Affiliated Hospital of Suzhou University, Suzhou, China; The Affiliated Hospital of Guizhou Medical University, Guiyang China.

出版信息

Pharmacol Rep. 2017 Dec;69(6):1206-1212. doi: 10.1016/j.pharep.2017.05.004. Epub 2017 May 11.

DOI:10.1016/j.pharep.2017.05.004
PMID:29128801
Abstract

BACKGROUND

Intracerebral haemorrhage (ICH) as a devastating form of stroke has remained a public health threat due to lack of FDA-approved therapy. Oxidative stress originated from blood cell degradation products plays a crucial role in the ICH pathogenesis. In this study we evaluated oleuropein, a potent natural antioxidant from olive, in a well-established rat ICH model from overall symptoms to detailed molecular mechanism.

METHODS

ICH model was established by collagenase injection to the brain of rats, which were randomly divided into groups with vehicle mock treatment, followed by treatment with different doses of oleuropein via daily intraperitoneal injection post-ICH for 3days. The overall neurological deficit, brain edema level and blood-brain barrier (BBB) integrity were then measured in different treatment groups. To understand the protection mechanism of oleuropein in ICH, BBB structural components ZO-1 and occludin, oxidative stress and MAPK signalling pathways were also examined.

RESULTS

Oleuropein treatment showed overall alleviation of ICH-associated neurological deficit and brain edema in a dose dependent manner. Consistently, it could preserve the BBB structure and attenuate oxidative stress as well as ICH-induced MAPK activation in brain tissue.

CONCLUSION

Our study suggests oleuropein could be used as a promising therapeutic agent for ICH.

摘要

背景

脑出血(ICH)作为一种毁灭性的中风形式,由于缺乏 FDA 批准的治疗方法,仍然是一个公共健康威胁。源自血细胞降解产物的氧化应激在 ICH 发病机制中起着至关重要的作用。在这项研究中,我们评估了橄榄中的一种强效天然抗氧化剂——橄榄苦苷,在一个成熟的大鼠 ICH 模型中,从整体症状到详细的分子机制进行了评估。

方法

通过向大鼠脑内注射胶原酶建立 ICH 模型,然后将其随机分为对照组(给予假手术和 vehicle 处理)和不同剂量橄榄苦苷治疗组(ICH 后每天通过腹腔注射给予不同剂量的橄榄苦苷,连续 3 天)。然后在不同治疗组中测量整体神经功能缺损、脑水肿水平和血脑屏障(BBB)完整性。为了了解橄榄苦苷在 ICH 中的保护机制,还检查了 BBB 结构成分 ZO-1 和 occludin、氧化应激和 MAPK 信号通路。

结果

橄榄苦苷治疗呈剂量依赖性地减轻 ICH 相关的神经功能缺损和脑水肿。一致地,它可以保护 BBB 结构,减轻氧化应激以及 ICH 诱导的脑组织中 MAPK 激活。

结论

我们的研究表明,橄榄苦苷可作为 ICH 的一种有前途的治疗剂。

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